By Helen Petousis Harris 21/02/2018 56

There exists a sustained brouhaha around the nature of the placebos used in the clinical trials for Gardasil.

The notion that some of the most rigorous vaccine trials ever conducted are questionable on account of their well thought out placebos is ill conceived at best. This is after over 270 million doses and huge epidemiological studies from all over the world comparing outcomes in vaccinated and unvaccinated (discussed ad nausea in my previous blogs). Guess what! Vaccinated have better outcomes than unvaccinated. Anyway, for the sake of anyone who is wondering about what all the placebo ruckus is about I have attempted to explain below.

What is a placebo?

A clinical placebo is a treatment that has no intended therapeutic effect. In a clinical trial a placebo could be a saline formulation which is typically inert when injected.  Or, the placebo could be the formulated mix of salts and left over impurities that are present with the vaccine under investigation minus the active ingredient (vaccine).

Vaccines often also have an extra added ingredient, called the adjuvant, which works as an immune enhancer.  The adjuvant is sometimes included in the placebo formulation.

Mind over matter is a very real phenomenon in medicine.

In using a placebo the investigators want to eliminate any thoughts, views, emotions and expectations as much as. Study participants will not know (they will be blind) to what treatment they receive, and often so will most of the investigators (double blind.

When you choose a non-active placebo

It has been well argued  that if there is an existing vaccine for a disease that it cannot be withheld from trial participants in order to test the new one against a placebo. That means if a new generation vaccine is developed for a disease, its effectiveness will need to be compared to its predecessor, and a placebo will not be needed. An example is the new Gardasil®9 vaccine. This new formulation contained nine instead of four different types of virus like particles. The pivotal trials compared the old and new vaccines head-to-head.

If you do not already have a vaccine against a disease then there is a case for using a placebo. An example of this was the first generation HPV vaccines. The formulated vaccine was put head to head with two different placebos. One was saline and the other the formulation mix minus the active ingredient.

What non-active placebo do you use?

There are two major considerations when choosing the placebo.

The placebo effect

The key objective of a placebo is to allow the participant to believe they have received the medicine being tested. In the case of an injectable vaccine the most common reaction is injection site pain, sometimes with minor redness and swelling. Often, the added adjuvant (immune enhancer) can be the main cause of the reaction and it is just doing its job. From a vaccinology perspective a mild to moderate injection site reaction is generally a good thing.

When you inject pure saline a very small proportion of recipients get sore arms where the injection was given.  A bigger proportion have a sore injection site when they get the placebo made from the formulation mix (missing the active vaccine). To make every injection as similar as possible in a vaccine study a good choice of placebo is the one that elicits an injection site reaction because the person is more likely to think they got the real deal.

If participants guess which group they are in (active versus placebo) then the study runs the risk of un-blinding. This can damage the integrity of the trial. Also, the investigators may guess which product is which just by looking at them. Simple differences like changes in smell, colour or viscosity could give it away.  It’s important that they appear identical to the investigator.

The role of the antigen

Another factor in placebo selection is the importance of understanding the role of the active ingredient (antigen or antibody generator). What difference to the reactogenicity and safety profile does the addition of the active ingredient play?

Many vaccine developers prefer to balance the safety profile (identified in the trial) by ensuring the products in the vaccine carrier are present in both the active and placebo products. This means both the active and placebo study arm should both have the same local reaction to the impurities and other ingredients such as buffers and adjuvants. Any additional reaction rates will be related to the active ingredient.

Some vaccine developers would prefer not to know if the active ingredient is the cause of the local reaction, and by not knowing can simply assert that they believe it is caused by the other ingredients and not by their antigen.

For a detailed list on vaccine ingredients and their function check out the Vaccine Ingredients resource from the Immunisation Advisory Centre.

The formulation without the active ingredient includes buffers, stabilisers and adjuvant. In the case of Gardasil there is sodium chloride (for tonicity), sodium borate (buffer), L-histidine (Stabiliser), polysorbate-80 (surfactant), and water for injection. When the active ingredient is added it is adsorbed to the adjuvant. One important question the investigators will want to answer is: What is the difference between a formulation that has just adjuvant and a formulation that has adjuvant adsorbed to active ingredient? Adsorbed means to adhere to via atoms, ion or molecules. In the case of vaccine adjuvant and antigen this is via the positive and negative charges on each (a positively charged antigen will require a negatively charged adjuvant).

Anyway, the choice of vaccine formulation minus the active ingredient as a placebo provides important data about the role of the active ingredient, which is the new kid on the block. Its behaviour when administered alone (without adjuvant in earlier phase studies) and in the full formulation is important.

Using the vaccine formulation mix minus the active ingredient is a normal practice in vaccine trials for the reasons outline above. For example, of three trials from different manufacturers for the same type of vaccine I am aware of, one used an adjuvant in the active formulation, and the adjuvant was not included in the placebo. Two of the three used the vaccine formulation mix in the placebo; the other trial used just saline as the placebo.

What was the placebo in the Gardasil trials?

There were two different placebos used. The one used in most of the controls included the vaccine formulation mix minus the active ingredient. A smaller group received saline with some impurities (L-histidine, polysorbate-80 and sodium borate). Therefore most of the participants who received a placebo would have had injection site reactions similar to the vaccine recipients, fulfilling the requirement of the placebo. Basically these placebos are stepwise progressions from the injection solution, injection solution with added adjuvant then the full formulation that included the antigen (active ingredient).

For a fuller discussion on the Gardasil placebos see my previous blog.

Arguments about the placebos – fact and logic

Some people argue that the Gardasil clinical trials are meaningless because:

  1. Most of the placebo recipients received the vaccine formulation minus the active ingredient and,
  2. The saline wasn’t really saline because it included L-histidine (an amino acid).

These arguments are factually and logically fallacious.

  • Fact: The placebos were true placebos by definition.
  • Arguing that the placebos contained adjuvant, therefore nullifying the study results, is logically flawed for the following reasons, among others:

First, just because a person imagines this is true does not make it true no matter how convinced they are. In know we live in a post truth world but I live in hope some people are still interested in objective evidence!

The burden of proof that there is a problem such as harm from using a non-saline placebo rests with those who claim it is harmful in the face of the wide body of evidence on vaccine safety. In other words it is a logical error to make a claim and assert people prove your negative (“prove these placebos are safe”) because you cannot prove a negative. This is otherwise known as evidence of absence. It is akin to proving that God does not exist, you cannot. You can only prove he does (away you go). It is up to the claimant to prove the claim that they are not safe. When you do this please do so with high quality epidemiological studies because that is the standard of proof required.

The fake placebo argument is a red herring and ignores all the evidence that supports the safety of both the vaccine and the adjuvant formulation. If you want to make an argument about the safety then you cannot ignore all the body of epidemiological data that support the safety in favour of ill-conceived laboratory studies. The premise that the various placebo formulations are unsafe is likely to be false, there is no data to remotely support this.
In arguing fake placebo-cover up-collusion-conspiracy I think the plaintiffs against HPV vaccine are running out of angles in the face of the tsunami of evidence in favour of safety but maybe I am just an optimist!

Many thanks to Nicole and Karin on this one.

56 Responses to “The brouhaha around placebo choice in vaccine trials”

  • The term placebo is clearly defined:

    It is a biologically inactive substance. Immunological adjuvants are not biologically inactive and they have known to be associated with serious side effects.

    They are by definition not placebos.
    A placebo (/pləˈsiːboʊ/ plə-SEE-boh; Latin placēbō, “I shall please”[1] from placeō, “I please”)[2][3] is a substance or treatment with no active therapeutic effect.
    A placebo (pluh-SEE-bow) is a substance or other kind of treatment that looks just like a regular treatment or medicine, but is not. It’s actually an inactive “look-alike” treatment or substance. This means it’s not a medicine.
    A placebo (or dummy pill) is an inert substance, typically a tablet, capsule or other dose form that does not contain an active drug ingredient.

    Using adjuvants for reasons of blinding is not a valid argument since drug safety studies are not required to use active placebos either. One could induce inflammation on the injection site by other means using various harmless substances(histamine), there is really no scientific reason to never use anything other than an adjuvant.

    The Gardasil trial had a saline group but in this group only mild side effects were measured making it impossible to measure serious adverse reactions.

    It is true that aluminum is everywhere around us including our food but aluminum particles in adjuvants are not the same as naturally occurring aluminum. They are metabolised in a different way, much of which is still poorly understood.

    see here:

    Proprietary formulations of aluminum particles without safety documentation can be used.

    As there is really no scientific reason for avoiding real placebos one has to conclude that the trial designs are used to make a product look safer than it is. A common practice in the pharmaceutical industry. Industry sponsored drug trials are often not 100% objective and honest and there is no reason to believe that commercial vaccine trials are any different.

    To learn more about dishonesty in for-profit science:

    • Skeptic
      You sat the term placebo is clearly defined, state it is a biologically inactive substance, then proceed to paste definitions that say no such thing. Do not confuse no therapeutic effect with biologically inactive. And, as Maurice has pointed out, I have explained this in the blog. I think it is fair to accept the general scientific consensus on the use of placebos in clinical studies because these are the standards that are globally accepted, adopted, and evaluated. This international consensus is arrived at by experience and reason.

      You are using fallacious arguments whereby you seem to be saying that anything that is not pure saline is not a true placebo because you have decided that that is the definition. This is a false premise. You then draw a false conclusion as you are saying therefore the vaccine is not safe. You have elected to ignore the huge body of evidence that shows vaccinated and unvaccinated are equally sick or healthy whichever way you want to look at it.

      Finally you use the strawman argument where you insinuate that i/we think industry sponsored drug trials are 100% objective. I/we hold no such position.

  • Skeptic

    A good analysis of “for-profit” attitudes is found in “Bad Pharma” by Ben Goldacre. I would recommend that you read it. I suspect that you won’t because it’s written by a real doctor.

    Medicine has been questioning the attitudes, motives and records of the pharmaceutical industry for decades; that questioning is not something new, even if it happens to be new to you.

    I would recommend that you follow up “Bad Pharma” with “Bad Science”, same author. It was written earlier but demonstrates how Big SCAM (Supplements, Complementary and Alternative Medicine) is even worse in it’s motives, attitudes and publication of records than Big Pharma.

    If you are a true sceptic, and not just trying to project a North American facade of one, you will know to apply your questions equally to all references and not just to cherry pick.

  • “I suspect that you won’t because it’s written by a real doctor.”

    Sweet shade dude. But what is your point? How is Dr Marcia Angell not a real doctor?

    Professor, was the saline trial part of the extra data that was submitted to the PBAC after its initial rejection?

    • Paul,
      Are you referring to the PBAC concerns about the cost of the Gardasil vaccine?

  • Skeptic/Paul,

    Problems with the pharmaceutical industry have been known by the medical establishment for many decades. Methods have been developed to reduce these problems and further methods are in development. The pharmaceutical industry has responded and there are currently less concerns than in the past although new concerns are arising.

    Angell appears to document some problems with the pharmaceutical industry and be shocked by them. It’s as though she hasn’t realised that others have been working on the problems for years if not decades.

    Goldacre, writing at least a decade later, documents the problems, the responses of the pharmaceutical industry, the changes made and their effects, and also proposes further methods to remove or minimise those problems, including options to prevent further problems developing. All duly referenced.

    Angell documents a problem. Goldacre documents past responses to the problem and their effects, reactions of the industry to those actions, further responses currently under way, and possible future actions by the medical and research establishments.

    As in the rest of science, it’s not good to cherry pick or to rely on outdated information. Multiple sources will give a more realistic viewpoint of where reality stands.

  • Professor. Cost-effectiveness, but yes. I went searching and from what I can glean from documents now no new clinical data was added, which is not my recollection. My apologies.

    Stuart mate, you do realise Skeptic and I are different people?

    Well since everyone’s recommending books, A Cup of Tea, A Bex and A Good Lie Down is a great read that taught me alot. Beware, its about 25 years old and written by a historian not a doctor. Feel free to link a better source on the subject if you know one.

    But to return to the subject at hand with a messy segue, one of the shiboleths that people trying to remove the APC’s from market faced, was arguments that its individual components were all known to be very safe for a long time. Not an exact analogy I know, but I am still failing to understand how adverse effects can be distinguished when the control uses an adjuvant. The argument that controls need to have a placebo that causes more adverse events so it can be an effective placebo to me seems counterproductive, cruel and unethical.

    What am I missing? Are there any reputable pro-vax PETA-like scientists that campaign for reform on this issue? I want to understand.

  • “Are there any reputable pro-vax PETA-like scientists…”

    PETA-like and Reputable are mutually exclusive conditions.

  • If you’re looking for books that might help you understand the perpetual ‘fussing’ over vaccines and vaccination, two I might recommend –

    Seth Mnookin’s exploration of the ‘vaccination debate’, The Panic Virus. I’ve reviewed it on Sciblogs here:

    If you want an (in-depth) look at the history of vaccines, you might try Arthur Allen’s book, Vaccine. The History of Vaccines website is another useful site. There are links to these two, and a few other sites, in my earlier Sciblogs articles, Immunisation then and now:

  • I do not know how you get away with repeatedly saying such BS! This webpage is sooooooooooooooooo unreputable. How do you call yourself a scientist? Surely you have the integrity not to do so with that at least. Please leave the science to the scientists. You repeatedly pull the wool over everyones eyes except professionals. A placebo is a saline solution FULL STOP! Quit making up BS to help maunufacturers cover up numerous side effects of vaccines.

    • Karen,
      Aside from the ad hominem, perhaps you should look up the word ‘placebo’.

      The word is from Latin and means ‘I please’. A placebo is used to make a person think they are getting the medicine. i have explained this clearly.

      Perhaps you could explain how saline would be used when testing a medicine that came in tablet form.

      Seriously, you are factually incorrect no matter how much you dislike that fact.

  • Hi Karen,

    You wrote, “Please leave the science to the scientists.”

    You realise that both Helen and I are scientists, right? (!)

    Can I suggest you try Seth’s book that I mentioned in my earlier comment. I’ve read it myself, and reviewed it in the link I provided. It’s a good effort by a journalist to get to the bottom of things. Libraries will likely have a copy.

    There are always a few people encouraging others to think various things about vaccines. A key problem with these people encouraging others to object to placebos is that is a distracting technique, encouraging people to not look at what the trials are doing. It’s the old magician’s ploy: here, watch my right hand waving about — and ignore what my left hand is doing. It’s better to try understand what the trials are doing.

    When testing medicines or vaccines, the comparison is are we better off with the vaccine or not? In the case of a new medicine or vaccine that might replace an older one, the comparison is is the new one better than the old one? In that case there’s no need for placebo tests because you just want to know if the new thing is better. By pointing at placebos, people are trying to distract away from that.

  • Hello Helen

    True to yourself, personally attack then get someone else to step in when the going gets too hard for you.

    Grant Jacobs you obviously think your doctorate makes you so much higher and mightier than everyone else. I realise you and Helen call yourselves scientists, but your manipulation of ‘evidence’ to only back up your agenda, is not science. It is not reputable or professional in the least. It is unproven propaganda. Note how I said “how do you call yourself a scientist”

    I do not need to look up the word “placebo”. I was taught what that is at university. A more reputable one than yours that permits staff members to put up blogs such as this. It is you who needs to learn the correct definition and terminology of a placebo.

    There was a fraud court case against Merck in part for advertising in their inserts that they used a ‘placebo’ when it fact they used what Helen says is a placebo. Merck ended up having to admit they did not use a placebo. How do you explain that away?

    I realise the vaccine industry is re-defining what science is and scientific validity to suit their own personal agenda of $$$$$$ and to downplay and eradicate side-effects and low efficacy; but that does not make it science. That is what is the actual “magicians ploy” that makes it hocus pocus.

    By pointing at placebos that are NOT placebos it highlights to people how BS the trials were, so it is about the trials. They do not use ‘placebos’ containing only the most dangerous component or another vaccine, without hiding a lot of side effects. With side effects you want to know if the vaccine has more adverse effects than to not have the vaccine. NOT how dangerous it is compared to another danger.

    Your sort of “scientists” have the gift of the gab. The gift to talk your way around all the BS with smokescreens, but that does not make it science. It makes it dogmatic propaganda manipulated to suit your own agenda. People like you make up your own stories to support your agenda and twist around reputable science to a pretzel. You are a thorn in the side or true scientists.

  • The testing of vaccines involves its side effects and efficacy to be researched prior to approval.

    Gardasil 9 would not have been approved if a correct placebo was used. They had to commit fraud to fast-track and get approval and pull the wool over the FDA’s eyes. What better way to make it appear the vaccine was not dangerous then to use the most dangerous component, the aluminum and another vaccine with all the risky ingredients, as “placebos” This could then make a benchmark that was on a par with the extensive side effects of Gardasil 9 so the sides effects could be brushed off as statistically insignificant.

    It is absolute BS that the vaccine has to be compared to another vaccine to assess the dangers. Merck performed a practice which if they follow and were not pulled up with in their fraud case, would escalate the dangers of vaccines as time went by. Merck crossed the line with their complacency of corruption and their smoke-screen of appalling scientific trials and how much propagandists would support the vaccine come hell or high water and how condoning people such as those from Immunisation Advisory centre, MOH, Medsafe etc. are happy to throw all professional conduct out the window to say the opposite of the transparency they had to use to the FDA

    I can see Merck will try and put it over people even more by having Gardasil 9 vaccine as the placebo for their next HPV vaccine, because of what the condoners turn a blind eye to and let them get away with. So they will base a fraudulent research upon fraudulent research upon fraudulent research….. The side effects will snowball without any recognition or acknowledgement at all of the vaccines being the cause if Merck and the condoners have their way.

    Hence the purpose of having a standard of NO VACCINATION as the benchmark, a saline placebo. One totally neutral universal standard of placebo for all.

    Here’s hoping their fruad case and the FDA keep them in check, or at least carry on publishing the information that shows how wrong the propagandist ‘scientists’ are.

    If one looks at the stories of why the condoners condone other placebos, pathetic!

    Recipients need to think they are getting the real thing. LOL In other words you want the recipients to expect adverse effects and will know they haven’t got the real thing if they don’t. Great idea to give them a dangerous ‘placebo’ then.

    It doesn’t take a doctorate for anyone to see what BS they are being told, if they just think about it rather then trust the condoning so called ‘scientists’ and health professionals.

  • The fact of Mercks trials is that they were testing far too many variables and not a single one had a population size or non-inter-relation that made any of the results scientifically reputable or conclusive. All in order to fast-track approval and then to guinea pig recipients after the money started rolling in in the hope that they could bribe and coerce enough “scientists” to give results in their favor.

  • “Perhaps you could explain how saline would be used when testing a medicine that came in tablet form”.

    OMG Helen Seriously!!!!!!!!!!!!!!!!!! How do you have your job position?

    Ummmmmmmmmmmmm really hard trick question that one. Sugar!

    I think you have anger and defensive issues. You get so hot under the collar with being cornered with truth that you dig yourself in deeper and deeper.

  • “A lie will go round the world while truth is pulling its boots on.”

    And this is so true when propagandists and the government with all their power sabotage, oppress and gag the truth and throw the boots over a cliff.

  • I’m sorry for the ad hominem Helen. I do not mean to stoop to your level. I am not the one authorities put on a pedestal to fleece others, and whom expects all to have my opinion or to be attacked. I do not get paid to have to not have a human response to your attacks, but to remain professional with high integrity at all times as your university should expect of you. ( although I see that is not the case given the university lets you put up this blog). But I do also understand how it is easier for me to be as you should be, as I have truth on my side and do not have to resort to attack and have understanding of how people respond when the truth is not on their side. So I apologise.

    • Karen
      I have not attacked you so please refrain from making ill-founded accusations. The University supports academics to speak freely on topics in which they are expert. Truth is determined by objective investigation, you cannot have your own truth, no matter how dear it is to you.

      Please refrain from the deluge of straw man arguments, sowing of discord and multiple postings, it is destructive and I will need to block you from participating in this forum if you continue in this vein.

  • The following is about one side effect Merck refused to study, but applies to all adverse effects.

    This article “Adolescent Premature Ovarian Insufficiency Following Human Papillomavirus Vaccination’” is on the National Centre for Biotechnology Information (NCBI) USA government website.

    It is authored by Dr’s Deirdre Therese Little, MBBS, DRANZCOG, FACRRM (Obstetrician for 27 years) and Harvey Rodrick Grenville Ward, Bsc(Med), MBChB, DMCOG, FCOG(SA), MMed (O&G), FRANZCOG2. Dr Ward is a member of Genea and Medical Advisory Committee of Baringa Private Hospital. He is a Fellow of The Royal Australian and New Zealand College of Obstetricians and Gynecologists as well as a NSW Board Certified Specialist. He is registered as a RANZCOG examiner and is a RAMUS mentor.

    In ‘Vaccine Components Used as Safety Study Controls’ they say:
    “The ‘placebo’ that formed the control selected for phase III safety studies of Gardasil (older girls) was the aluminium adjuvant present in the vaccine solution, amorphous aluminium hydroxyphosphate sulfate. The selection of aluminium as a control in vaccine studies is AT VARIANCE WITH THE SCIENTIFIC PRINCIPLES OF A CONTROL. The ‘placebo’ in the only controlled study of very young girls was the remainder of the vaccine carrier solution: The ‘placebo’ used in this study contained identical components to those in the vaccine, with the exception of HPV L1 VLPs and aluminium adjuvant. It contained 50 µg polysorbate 80 (polyoxyethylene sorbitan mono-oleate also known as Tween 80), 35 µg borax, 9.56 mg sodium chloride, and 0.78 mg l-histidine”.

    “Safety studies identified at licensing (there have been no post market trials done) did not compare HPV4 with NORMAL SALINE CONTROLS. The second ‘placebo’ contained several substances together with saline”.

    What the authors are saying here is that in trials by MSD one ‘placebo’ of aluminium adjuvant one of the most dangerous ingredients in vaccines, was used on older girls; and the less dangerous ‘placebo’ was applied to younger girls.

    MSD did not conduct the research on the younger girls themselves, but rather poached the safety results of another researcher whose ‘placebo’ contained all the other ingredients including another of the dangerous ingredients, but not the viral active parts and aluminium.

    There was NO double blind placebo. Not even a single blind placebo applied!
    Dr’s Little and Ward explain the significance of this:

    “Published safety studies only compared HPV4 vaccine with its own components. This may be significant since injected substances in both ‘placebo’ control arms have either a suggested association with autoimmune ovarian damage or known direct ovarian toxicity. Completed vaccine and ‘placebo’ courses each administered 675 μg of aluminum to older girl safety study participants; or components including 150 μg polysorbate 80 to all 9- to 15-year-old safety study Participants””.

    • Karen,
      The article you provide is a description of three cases of ovarian dysfunction that apparently occurred following vaccination. I assume the authors are well qualified to diagnose this condition. So, using science, what would happen now?

      To test the hypothesis that a vaccine increases the risk for this condition we need to assemble exports not only in the condition but also pharmacovigilance and epidemiology among others and design as study to examine the risk in vaccinated people and compare this with unvaccinated because of course if half the females in this age group receive the vaccine then all things being equal half the cases will occur in vaccinated people.

      It happens that there are a number of studies that have examined this hypothesis in large population studies which have all concluded no association. You could access the periodic reviews by the WHO, links to studies are provided. These reviews represent the collective position of experts with a diverse range of expertise from around the world, none who are employees of pharmaceutical companies.

      You need to stop throwing in the red herring placebo argument. Grant has pointed out this error in logic to you and it has nothing to do with any potential causal association with this ovarian claim, or any others.

      I will request that you cease inundating these comments sections with non-constructive declarations as you clearly have no interest in engaging in an objective discussion.

  • Hi Karen,

    A couple of corrections, and a few thoughts.

    get someone else to step in when the going gets too hard for you

    Helen did not do this. I wrote of my own accord, on my own initiative.

    It might help to know that I, Alison, and a few others were writing on vaccines in this forum for several years before Helen joined Sciblogs. I write less often on vaccines now, but I’m still open to the topic. In particular, I still write on the erroneous (and rather sad) vaccine-autism claims. (Autism is dominantly genetic. So-called ‘complex’ genetics is an old interest of mine from a post-doc using genetic linkage work). My most recent post on that is here,

    Grant Jacobs you obviously think your doctorate makes you so much higher and mightier than everyone else.

    Could you please not make strawman characterisations of people? It’s not helpful.

    I wrote nothing like what you suggest here! What I did write was that it’s unlikely that the specialists involved are as stupid as some anti-vaccine promoters try to make out. A few anti-vaccine groups or anti-vaccine advocates like to encourage others to do a sort of finger-pointing where experts are, somehow, missing the absolutely obvious on the things they are involved in. That has these anti-vaccine promoters doing not much more than a conspiracy theory approach.

    It’s far better to try understand what is being done, and why.

    Put another way, writing “but, but” only works if you first understand what you’re putting the “but”s against. You have to first learn what is being done, before you can consider if there might be any problems.

    I realise you and Helen call yourselves scientists, but your manipulation of ‘evidence’ to only back up your agenda, is not science. It is not reputable or professional in the least. It is unproven propaganda.

    Sorry, but this is strawman stuff. Tossing around characterisations isn’t going to help you sort out if what is being done is sound or not. Trying to understand what is being done might.

    Note how I said “how do you call yourself a scientist”

    Sure, but I wrote in response to you writing, “Please leave the science to the scientists.” I quoted this before replying to make it clear what I was replying to. You said that science should be left to scientists, and I pointed out that Helen and I are scientists.

    As I was saying to you earlier, you’re not going to resolve if vaccines are safe or not by repeating claims those opposed to them encourage you to say. Similarly “raining” comments here won’t sort it out for you, either.

    What will help is to try understand what is done, and why.

    Put another way, you have to understand before you can make a critique.

    I rather like turning a Bob Dylan quote into a little mantra for this: ‘You can’t criticise what you don’t understand,’. Of course Zimmerman was referring to parents’ sons and daughters, but it’s also a more general truth. You can’t critique something you don’t understand.

    Perhaps then, try understand why it’s being done the way it is first? You might then be in a position to see if there are any issues.

    I pointed out in my previous comment why the focus was on the younger age group.

    I also explained earlier (in another post) why focusing on placebos is a distracting technique some anti-vaccine groups encourage: it distracts away from what was actually done, focusing people on a (made-up) “but, but”. Better to start with what is being done, and understanding why, then you’ll know what vaccine specialists are really not being silly.

    I’d encourage you to try the suggested reading I mentioned earlier.

    Finally, can I suggest you limit yourself to, say, a couple of comments a day? You’re spamming this forum.

    I’m not going to read all your comments (too many, and too many loose claims), but just one point:

    MSD did not conduct the research on the younger girls themselves, but rather poached the safety results of another researcher

    The whole point of scientific publications is to make the results available so that others can use them. There is no ‘theft’ in that, this is what science is supposed to do. All scientists use the work of others. You’ll know the cliché sitting on the shoulders of giants: all scientists build on other scientist’s work. There’s little value in repeating work merely for the sake of repeating it unless something suggests a need for replication.

  • Grant

    I have noticed other blogs by Helen in which you come to her rescue as soon as someone is cornering her with truths. Don’t pretend it is just this one and I do not know why you are changing the subject and bringing in other lies of vaccines such as autism link (which is only partly genetic for some people).

    You took my sentence of leave it to the scientists out of context. All sentences should be read in context with the paragraph they are in. Do you now agree? It seems all you accuse me of is you.

    As for your strawpeoples!!! Helen and yourself use personal attack and give opinion. You tell me that my cutting and pasting experts well above me in quals to conclude in that field is for some reason unreputable, and yet you say it of my opinion too? So should everyone never leave comments on these blogs unless they are full of praise to Helen and nod their heads just like the inert dogs you see on car dashs?

    I fully and deeply understand what is being done with vaccine ramming, it is especially and readily identifiable with the Gardasil vaccines. Therefore you condescending judgements of me is totally incorrect and you should not do so given you do not have the slightest clue what my training and qualifications are in.

    I have never mentioned anything about having to start with a younger age group and do not know why you keep going on about that.

    There is absolutely need to repeat research, when it is pharmaceutical companies drawing up the conclusions. It is independent research that gives reputable results.

    Your entire post above is distraction, strawman, changing subject. Even if I was to post everything I have in my mind the moment I read such BS in a blog over several days, you still would not be able to answer my concerns professionally. You do not have the truth on your side to do so, hence the good ole vaccine rammer techniques you use.

  • Hi Karen,

    Sorry to be to the point but your latest is out of line, it’s straight-out attacking me and doing little else. For my part, I’ve gone out of my way not to. I’ve just read back through my comments here, and none ‘attack’ anyone. It’s just not helpful to make me out to be doing something I’m not.

    It’s your call, but from (long) experience until we engage with, and understand, something we can’t judge it. That’s essentially a tautology – one reason I keep coming back to this. If you want to know if vaccines are safe or not, you’ll have to first properly understand what was done, and why. If you don’t, you’ll end up defeating your own aim, as it were, and there’s little sense in railing at me for that! I’m only someone trying patiently to point out a more useful direction for you.

    While I’m on suggesting how to tackle things, it’s wise not hold too tightly onto things that confirm to your beliefs. It’s better to be wary of them because they conform to your beliefs a bit too well. It’s a useful trick that prevents us from fooling ourselves about something.

    If you knew me better, you’d know that when I wrote my (older) vaccine posts, I took the objections people made and traced right back into the literature to make sure they might not have a point. It took me a lot of time. None of them were like they thought it was, although I could sometimes see how they’d gone wrong.

    Just quickly about this –

    I have never mentioned anything about having to start with a younger age group and do not know why you keep going on about that.

    I replied to a point you made, and I quoted that so you’d see that. The reason I’ve repeated this point is that it’s illustrative of what you’re not doing, that you want to be trying to understand what is being done first. All they’ve done is test for the age groups that the vaccine is (initially) for.

    The main purpose of the HPV vaccine is prevent cancer (mostly cervical cancer) by preventing HPV infection. Given that, the aim is vaccinate pre-teens through to teenagers in the first instance. Naturally you test for what it is that you intend to do. They’re not intending to vaccinate those over 65; there’s no point in testing for that. That they didn’t test over-65’s is not a “fault”, it’s just a statement that group of people weren’t tested – which is what you’d expect as they’re not a focus for this vaccine. (By contrast you’d expect older people to be tested for an influenza vaccine, because they’re a focus for that vaccine.)

  • Grant it is the vaccine “research” people need to be wary of as it stinks of rotten rat a mile away. But of course you have to have the scientific training as so many of us trained in science and now speaking up against the manufacturers vaccine “research” can identify.

    You have personally attacked, but it would not be the only thing you are in denial of. I.e judging I have no understanding of science or trials, that I hold on tightly to my beliefs on vaccines, that I set up strawmen when in fact I have very much stuck to this blog topic and it is you who has tried to smokescreen and detract my replies etc etc.

    All your judgements are incorrect.

    A scientist normally would stand by the most reputable evidence of that time, until it is dispelled by equally reputable evidence on the scales of reason. I have put forward what I currently believe and have asked Helen for evidence that you both proclaim over-rides the most reasonable conclusions I have at this given time. However, you have not come forward with that. You have just got personal and refused to put your money where your mouth is.

    I have a very comprehensive understanding of how the Gardasil 9 trials were conducted. You have no right to tell me repeatedly I do not. That does not make you any more knowledgable just to parrot that over and over. You have shown you like to judge and disrepute people with personal attack, rather than with evidence; and then victimise your victim when they point out what you do and write in their defense to justify yourself. These are so tactics of people who do not have the truth on their side, and is very common with government authorities on vaccines. I do understand you do not have the evidence.

    I do not understand what you mean by strawman, but I do know you are saying of people who do not agree with vaccines, what the vaccine rammers and propagandists are themselves. With you lot it really is as said “we do not see things how we are, we see them how we are” by Anais Nin, with you lot. Your useful tricks do not fool yourselves about something, but most definitely are utilized to fool others about something. If Helen really believed what she was saying she would be able to post credible evidence to back up her statements.

    That is quite arrogant of you to think you can judge how you know how others go wrong when they see through the likes of all at Immunisation Advisory centre, the so-called ‘science’ of the agenda focused, pre-concluded, biased ‘research’ of the vaccine companies etc You do not have a clue about me, my training, my qualifications, what I am doing with this information, my sources, my position, my integrity, etc etc My sources are a heck of a lot more qualified and reputable than yourself or Helen, on HPV and Gardasil vaccine.

    I’m only someone giving you vaccine rammers/propagandists a chance to prove to me that what Helen says on this blog is based upon reputable scientific evidence; not pharma companies or government, WHO etc

    With that last point you are making a strawman of, the Gardasil vaccine, in which you go on and on that it only has to be released for the group they have done research for. Take a look at Page 1 on the NZ Datasheet. There you will see it clear as day says:

    Therapeutic indications
    “GARDASIL 9 is indicated in females aged 9 through 45 years* for the prevention of cervical, vulvar, vaginal and anal cancer, precancerous or dysplastic lesions, genital warts, and infection caused by Human Papillomavirus (HPV) Types 6, 11, 16, 18, 31, 33, 45, 52 and 58 (which are included included in the vaccine).

    And yet on the same document: “Currently there are no data from studies of GARDASIL 9 relating to females over 26 years of age” (pg 2).

    That’s not looking too much like Merck have released it only for adolescent girls until they can have research results for older women further down the track does it? This strawman looks more like he is saying Merck approve it for all under 45 year olds regardless that is was NEVER tested for over 26 year olds. How does that defeat your own aim when you you dogmatically hold firmly to confirming your own beliefs?

    • After two warnings I am arranging to have Karen blocked from these discussion forums as she has refused to rein in the continual disrespect to participants and straw man arguments. Her most recent comments have been deleted for these reasons. The behaviour is trolling, with some 40 comments, most of which are clearly an attempt to provoke some kind of emotional response.

  • Please unblock Karen. What she is saying is valuable and interesting. I wouldn’t call it trolling personally. It’s great to have someone on the other side of the fence pointing out the problems with these trials, you have to admit her points are valid and worthy of further discussion? Obviously she is passionate about this subject so sometimes you need to brush over the things you see as ‘straw man’ comments and focus on what she’s actually trying to argue so that some progress can be made, and not to appear yourself as making ‘straw man’ comments?
    I’m just a casual untrained observer, but this discussion is certainly interesting, and valuable if you can all manage to keep focus on the topic at hand.

    • Hi Kelli

      Karen has been able to post some thirty comments across these blogs over a period of a few days, there is probably an equivalent amount that have been blocked from the point that I said she would be blocked. I have had enough of the behaviour and gave two warnings first. Many of her questions have been responded to. Blocking her is not censure ship. The reason for blocking her is because she is trolling. She has rejected every response provided here. I suggest if she has more to say she should set up her own blog. Here we use the scientific method and objective discourse to find truth.

      Karen says:

      “You also use emotional coercian, manipulation, intimidation and blackmail with advertising showing children who have suffered from the disease itself; whilst conveniently ignoring the many more permanently injured or killed by the vaccines; or the fact that many of those suffering with the disease do so despite vaccination and/or because of it.
      But when it comes to professional scientific debate, you can not come up with reputable science to back up your claims.”

      This is a serious allegation and it would be a terrible thing to be guilty of this sort of behaviour. My issue here is that there are no children killed by the vaccine and that is a fact. That fact is accepted by the global scientific community and I have provided the evidence ad nauseam throughout these blogs. If that evidence is insufficient there is no conversation to be had because if someone cannot accept the science then we really cannot have a discussion about it. Karen has decided that the global scientific community including the World Health Organization are all guilty of some pretty awful things:

      “Immunisation Advisory Centre, Medsafe, MO’H’ etc always have the time to use tactics such as gagging, oppression, refusing government services, firing doctors who speak out, DEFAMING those who say the truth, personal attack, intimidation, arrogance, INCITING OTHERS TO HATE, sabotaging websites, browsing, computers, USB sticks etc etc”

      If you have a specific comment, concern, or question then that is very welcome. You can expect a response based on the best science based evidence I have. Beware the internet, it is full of pseudoscience.

    • A commenter was blocked over the holiday weekend following a number of comments that contained personal attacks and potentially defamatory remarks, both of which are in violation of our comment policy:
      I have now reinstated the user’s commenting privileges, but all comments from this person will require manual moderation by an administrator – this may result in a delay depending on an admin’s availability to approve comments. If comments continue to breach our comment policy, the user will be permanently banned.
      – Sciblogs admin

  • Hi Kelli,

    I’m not a fan of outright blocking,* but you have to admit Karen has been given plenty of opportunity to write without slagging at people, and that she’s been encouraged not to.

    (*FWIW: I have written about vaccines too, and I’ve only ever blocked one person on my blog [for trying to go around the blog to attack me privately].)

    While I’m writing: as a practical matter it’s hard for other readers to follow other conversations at Sciblogs if one person comments repeatedly in serial fashion (as she has).

    It’s great to have someone on the other side of the fence pointing out the problems with these trials, you have to admit her points are valid and worthy of further discussion?

    Very little of what she has written is “pointing out the problems with these trials”. What she is doing is holding up statements and making them out to be ‘problems’ – it’s an important difference. She may well be doing that innocently, perhaps mislead by others, but there is a difference.

    One core problem is not first understanding what is been done first. The things that haven’t been done are are mostly straight-forward if you first understand what is being done.

    Rather than address the far too many claims she made, I used one example. She presented not testing over-65’s as some sort of “fail”. I explained that vaccine is intended for the young, there’s little sense in testing a group it’s not intended for, and that if later it’s wanted to be applied to that age group it can be tested on them then.

    Obviously she is passionate about this subject so sometimes you need to brush over the things you see as ‘straw man’ comments

    There’s a difference in being passionate about a subject, and making strawmen of others! (There’s an example on this forum actually; one commenter is maddeningly keen on a very particular bit of dodgy “science”—let’s say it’s his little obsession!—but while he jumps on it at the slightest opportunity, you don’t see him making personal attacks. There’s a difference. I have to admit I’m not sure it’s that much better!!)

    Yes, we can all ignore the attacks (or ‘trolls’ baiting attempts’, depending on your point of view) — for a while. I do, but if the person won’t stop it makes discussion impossible. (My solution is usually to stop replying to them if the persist too much; often they then try turn that around to ‘accuse’ me for not replying!) Realistically, you can’t discuss with people like that. What you can sometimes do—not always successfully—is show the problem to the ‘silent’ readers in your replies to them – it’s a common approach with these contentious topics.

    and focus on what she’s actually trying to argue so that some progress can be made, […] and not to appear yourself as making ‘straw man’ comments?

    To the first, what I did eh, and to the second, unfortunately anyone can scream out that “I am being attacked”, when they’re not; they just have to make the (empty) accusation.

  • @Helen

    I made the claim that a placebo is an inert, biologically inactive substance per definition. I do not say anything that is not saline is not a placebo. I say anything that has known biological effects is not a true placebo.

    Here again, examples how a placebo is defined in clinical trials.
    Placebo – An INACTIVE substance or treatment that looks the same as, and is given in the same way as, an active drug or intervention/treatment being studied.
    “Things like sugar pills, that look like real treatments but in fact have NO PHYSICAL EFFECT are used to create “blind” trials in which the participants do not know whether they are getting the active treatment or not, so that physical effects can be measured independently of the participants’ expectations”
    “A placebo is a ‘dummy’ treatment, such as a sugar pill, that looks the same or is used the same way as the interventional substance, but that has NO KNOWN HEALTH EFFECT.”
    Placebos are INACTIVE substances or interventions, most often used in controlled studies for comparison with potentially active drugs.

    So you can clearly see that it is INACTIVE, NO HEALTH EFFECT, INERT.

    An adjuvant has a known biological effect. It is used because it has known biological effects. If it had no effects they would not use it obviously. It is according to the definition not a placebo.

    A proper placebo, according to the definition would be saline solution or water or a sugar pill or homeopathy. An adjuvant is not a placebo because it is not inactive.


    I will not read it because it is not written by a real doctor? I had linked to a book written by a former editor in chief of the New England Journal of Medicine, a MD.

    Why is she not a real doctor? Ben Goldacre is a psychiatrist and journalist. I do not think he is even active as a doctor anymore. What is a real doctor? Someone who writes something that you like to hear?

    I can not believe we argue about what a doctor and what a placebo is. The editor of a medical journal is not a real doctor and a biologically active immunological adjuvant is a placebo?

    So black is white and white is black? I am not convinced.

  • So here are the placebo groups with the number of patients from the Gardasil trial (approximate numbers):

    8000 Gardasil group
    5000 Placebo Group (Amorphous Aluminum Hydroxyphosphate Sulfate)
    500 Placebo Group (Saline)

    As you can see the numbers in the saline group, the only true placebo here are really small compared to the other groups. It has been marketed as placebo controlled while it really is not. With the saline group being so small it would be hard to get any meaningful understanding of side-effects that are related to the adjuvant they use.

    From what we do know the adjuvant does not leave the body quickly, it can persist in the body for weeks, months or perhaps even years. We do not know exactly because it has never been studied. We took the data and information about aluminum and assumed that the adjuvants would have exactly the same side-effect profile and properties, something that might turn out not to be true.

  • This article perfectly sums up the circular logic that underpins tortured vaccine “science”—an edifice built entirely upon assumptions and wishful thinking.

    Author: proving non-saline placebos are safe is impossible, because “you can’t prove a negative.” Therefore, burden is to prove they’re unsafe.

    Okay, so the most logical way to do this: compare the active AL adjuvant to a genuine (inert) saline placebo, and measure the outcomes. Åuthor: “But this premise is likely to be false! There is no data to remotely support this!”

    There is no data, BECAUSE THIS SPECIFIC HYPOTHESIS HASN’T BEEN TESTED. You cannot arrive at this conclusion, again, BECAUSE IT HAS NOT BEEN TESTED. You know… that pesky little process called “science?”

    • Crd,
      What would an experiment comparing a vaccine adjuvant with saline tell us about the safety of a vaccine?
      If you are proposing a randomised controlled trial that tests a vaccine ingredient in order to demonstrate the safety of a vaccine you may like to consider that this is logically the same as testing the consumption of formaldehyde against placebo in order to establish the safety of an pear.

  • I have been conveyed a link to this discussion, and am the lead author of the above quoted paper reporting a case series of idiopathic premature ovarian insufficiency following Gardasil® in teenagers and examining ovarian safety research.
    If I may be permitted to join your discussion, this comment requires correction. No studies published to date have examined the hypothesis of a connection between Gardasil ® and ovarian dysfunction. Could you possibly please provide your references?
    The WHO site you refer to reviews the Arnheim-Dahlstrom Denmark and Sweden study, which excluded observation of any ovarian disorder from its specifically named list of conditions observed, as well as other studies which looked at emergency department presentations, eg Klein, Hansen, Chao et al. Missed periods, irregular periods and amenorrhoea do not present to accident and emergency departments, and were therefore not assessable in these studies. A subsequent study not referred to by WHO (McInerney et al) has looked at fecundability only, focusing on ability to conceive per cycle after Gardasil® and ‘correcting for irregular periods’, which disabled the study from reporting on symptoms of premature ovarian insufficiency.

    Original Gardasil ® clinical trials did not include any participants of the vaccine target age-group in Phase III studies, which were V501- 013 and 015 etc. The vaccine target age- group were only included in Phase II trials V501-016 and V501-018. The 016 trial had no placebo. The 018 trial used a vaccine excipient placebo at odds with the usually accepted vaccine principle that the placebo should lack the substance being tested. The protein containing substance was named saline, about which I formally complained to the Therapeutic Goods Administration of Australia. I received the following reply:
    Our Reference: RI 5/554600
    Dear Dr Little
    Subject: Gardasil Product Information Safety Trial Data
    Thank you for your correspondence of 20 June 2015 regarding the representation of Gardasil’s safety trial information in its Product Information (PI).
    Following a review of the PI, I have been advised that your observation about the composition of the placebo in study 018 is valid and that the current information is a misrepresentation of the situation. That is, that the current reference to the placebo being ‘saline’ misrepresents the actual placebo used in protocol 018.
    As a result of this review, the sponsor, Merck, Sharpe and Dohme Australia Pty Ltd, have been requested to amend the relevant headings in Table 11 and Table 12 of the PI from ‘Saline Placebo” to ‘Placebo***” and under each table include an additional footnote stating the composition of the (non-aluminium containing) placebo. Merck have been asked to undertake this amendment when they next revise the Product Information.
    Thank you for bringing this matter to my attention.
    Yours sincerely

    Dr John Skerritt
    Deputy Secretary
    Therapeutic Goods Administration
    Department of Health
    3/ August 2015
    This unfortunately becomes problematic when attempting to compare reported outcomes between vaccine and placebo groups for potential ovarian problems, since the rat ovary-toxic substance polyoxyethylene sorbitan mono-oleate (polysorbate 80) was present in the ‘saline’ placebo as well as in the vaccine in equal quantities (50 ucg in each of the three doses administered). The only published studies reporting menstrual function post vaccine were unfortunately mere observational studies. They found 48% and 45% of women reporting new onset menstrual disturbance following Gardasil vaccination (Danish Med Journal 62:1-5; Drug.Saf. DOI 10.1007/s40264017.0574-6 Shinzu University Clinic). It is indeed the absence of any Gardasil ® safety trial placebo ‘which lacked the substance

    • Hi Deirdre
      Thank you for your comment. You comment that I have quoted your case series paper on this post (the brouhaha around placebo choice). I cannot see where I have discussed ovarian insufficiency here. I assume you refer to my blog on “HPV vaccine does not destroy fertility”? Sorry I cannot find the comment thread but I have certainly discussed it.

      I have referenced the WHO Global Advisory Committee June 2017 meeting summary several times as this is the most recent GACVS review of the safety of HPV vaccine and ovarian dysfunction was discussed in light of new data. The meeting conclusions are in that publication. The committee is made up of fourteen international experts across a range of disciplines related to vaccine safety. All had the opportunity to scrutinise the data, and all contribute to the conclusions.

      I am not going to comment further here on the placebo other than to reiterate there is no reason to think that the placebo’s used in the Gardasil trials affect fertility. The question here I think is around the potential for ovarian dysfunction following receipt of HPV vaccine. We have two key lines of evidence to indicate HPV vaccine does not damage ovaries or fertility.
      1. If the vaccine affected fertility through any mechanism then were would see lower fertility, pregnancy, and ultimately infants, associated with the vaccine. This is not the case and safety with pregnancy and birth outcomes has been demonstrated and published.
      2. The GACVS summary notes that new data that now included ovarian insufficiency as an outcome was presented at the meeting and reviewed. No safety concerns were noted. Some of this data is from the US Vaccine Safety Datalink. It has since been presented at conference and accepted for publication in a high ranking journal. We will all have to wait for it to be published. However, the previous work from the Vaccine Safety Datalink looking at the Safety of HPV vaccine is impressive and published so you can see the type of methodology used and what you might expect from the newer work. The more recent study is of course based on many more doses. Here is an example

      I would strongly disagree with the insinuation that observational studies are ‘mere’. These are in fact far more powerful in detecting rare outcomes than a placebo controlled trial and modern epidemiological tools combine with large populations can deliver robust results.
      In fact it is the large observational studies that allow us to compare outcomes in vaccinated and unvaccinated people. A well designed cohort study can be as robust as a clinical trial when it comes to assessing vaccine safety.

      Your assumptions about polysorbate are unscientific. You cannot apply laboratory experiments in rodents, particularly when the model its self is inappropriate, and suggest this has any relevance to vaccine safety. Human data do not support any of this.

  • Readers:

    When we are dragged back into a thread like this by a statement such as this from crd. (Becoming common here, certainly not a question) it is worth rereading what Helen said in the original blog. Please scroll up and read the original statement.

    In this case the key statement is,

    “The notion that some of the most rigorous vaccine trials ever conducted are questionable on account of their well thought out placebos is ill conceived at best. This is after over 270 million doses and huge epidemiological studies from all over the world comparing outcomes in vaccinated and unvaccinated (discussed ad nausea in my previous blogs). Guess what! Vaccinated have better outcomes than unvaccinated. “

  • Good afternoon Helen,
    Your comment regarding Premature Ovarian Insufficiency was made here at 4.15 on the 27th March:
    1. ‘It happens that there are a number of studies that have examined this hypothesis in large population studies which have all concluded no association’ and

    2. ‘You could access the periodic reviews by the WHO, links to studies are provided’.

    You wrote this referring to my article which had been cited immediately above ‘Adolescent premature ovarian insufficiency following quadrivalent human papillomavirus vaccination: a case series seen in general practice’. Could you please supply the references for statement 1.
    The WHO statements to which you refer do not have ‘links to studies provided’ on this matter (Gardasil ® and POI) because there aren’t any as yet. As I have shown above, the studies WHO have referred to do not present, report on, discuss or have any capacity to evidence ovarian safety post Gardasil® vaccination.
    There is no ‘new data’ to be referred to since there is no new research except for the observational studies I have already cited which do indeed report 48% and 45% onset of new menstrual irregularity following Gardasil® vaccination.
    I am heartened to hear that you place great weight these observational studies ‘more powerful in detecting rare outcomes’ which do suggest possible ovarian alteration following vaccination, and thus mandating further rigorous research. They cannot prove or disprove the hypothesis of ovarian insufficiency post vaccination, however. This level of research would have required long term observation and a placebo control in accord with usual scientific principles that ‘a placebo must lack the substance being tested’.

    3. ‘You cannot apply laboratory experiments in rodents, particularly when the model its self is inappropriate, and suggest this has any relevance to vaccine safety’.
    Early toxicology studies are actually required to be done on rodent mammals, Helen, looking for any indication of potential toxicity. Rat studies are an important underpinning feature of pre-clinical research. That is precisely why rat studies or other rodent toxicity studies were and are part of the preliminary licensing process. This is because it does indeed have a great deal of relevance to vaccine or other medication safety for humans.
    It had previously been found that all injected IP doses of polysorbate 80 tested – from 1000ucg to 10,000ucg – were equally toxic to rat ovaries (Gajdova et al). No ovary-safe injectable dose has yet been established. It is therefore perhaps unfortunate that the rats studies in Gardasil ® trials did not have a histology (microscopy) report presented of the rat ovary after Gardasil®, but supplied only a histology report of the rat testis

    4. ‘there is no reason to think that the placebo’s used in the Gardasil trials affect fertility’.
    The Gardasil placebo contained 50 ucg poysorbate 80 x3 doses. As the TGA has affirmed in the letter above, this substance was in the placebo. Again, see Gajdova et al Delayed effects of neonatal exposure to tween 80 on female reproductive organs on rats’. Ovarian toxicity at much higher doses would not be such a concern if a safe dose had ever been established of the injected form. The placebo control was ‘misrepresented’ by Merck Sharp and Dohme as saline. This is pretty well established now. Polysorbate 80 was also present in the ‘aluminium placebos’ of phase III clinical trials, but its presence there was not declared in the published phase III trials. Misrepresentation of placebos has previously been considered medical misconduct.
    POI takes 5 years to diagnosis in 75% of young women. 25% remain undiagnosed after first presenting with this problem, and the condition is invisible on hormonal contraception. This will make the VSDatalink more unreliable. Only 33% of women report amenorrhoea.
    I was a little surprised you did not want to comment further about placebos since your article is entitled ‘Brouhaha around placebo choice’. Discussion of placebo controls must always be scientific, transparent and factual.

    • Deidre,
      Not sure you read my reply. I said that the new data was presented and reviewed but not yet published. I also mentioned the type of study with an example to illustrate that it would be indeed capable of investigating ovarian dysfunction. WE will have to wait for the VSN latest study as I said but it is robust and as the GACVS noted shows no causal relationship. Also, certainly there have been no signals in the Vaccine Adverse Events Reporting System (Arana, Vaccine, 2018). Current consensus statement from CDC here.

      I think Grant has made some good points that I agree with. To add to that, are you suggesting that the global body of experts on vaccine safety and vaccine epidemiology, and vaccine development and testing, and the global regulatory agencies are all deluded about the nature of the placebos in the Garadasil trials?

      The illogic appears to go: Large amounts of a substance are injected into the peritoneal cavity of a rodent and the rodent babies evaluated for abnormalities, therefore vaccines that contain this ingredient in tiny amounts must be unsafe.

      You are making an argument from ignorance – argumentum ad ignorantiam a common logical fallacy. I agree with the arguments presented by David Gorski and rather than reiterate here is a link instead to his comments.

      BTW, we inject HPV vaccine intramuscularly into humans. We are also most interested in the safety of the full formulation, a matter that has been and continues to be intensively studied and despite extensive efforts we had failed to find safety issues of concern.

  • Just brief comments from the side as it were. I’m a biologist, without a dog in this fight.

    Deirdre Little’s paper is a case study. Leaving concerns about her case study aside, cases studies cannot imply cause; many of her statements over-reach. (I’m being polite. I’m also generalising to save readers a long, convoluted reply.)

    In my opinion her case study has obvious failings. I may write a short take on this later on my blog—no promises, sorry, I have other things I have to do. I’m struck by that her case study one of the ‘best’ examples of post ergo proctor hoc I’ve seen. (False logic that something has likely caused something else because one followed the other.) In particular, her case study doesn’t mention some relevant things, or appears to want to walk around them. As a result it fails the young women who experienced this condition. (As an aside, it’s possible Little’s focus on the vaccine is influenced by religious views—I understand that Dr Little is an advisory board member of a ‘Family First’ type organisation.)

    Her case study (and at least one earlier work by her) have previously been ripped apart by others e.g. by Dr. Gorski, an oncologist, and elsewhere. My style is different, but the points raised are worth noting. Her earlier claims were also answered by the Australian Therapeutic Goods Administration.

    I’m interested in another way. One of the things my reading & writing focuses on is genetics. Many instances of this and related conditions have long been noted to have a genetic cause, with causative mutations in genes identified, and so on. Her case study does not appear to consider this, and I notice it hasn’t been mentioned here either.

  • @Helen
    Your comparison is silly on multiple levels, and makes an error commonly found in vaccine safety discussions. Not only does the route of delivery (injected AAHS vs ingested formaldehyde) make a huge difference in how these substances are processed, accumulated, and eventually eliminated from the body, an adjuvant is DESIGNED to trigger an immune response. That’s its purpose… it’s an active ingredient. Scientists do not understand how Gardasil’s adjuvant works (see Cochrane’s proposed review of aluminum adjuvants, this point is clearly reinforced)—only that its observed function is to magnify the desired immune response. Not using a true placebo when studying a vaccine containing an AL adjuvant compound WHOSE BIOLOGICAL MECHANISMS ARE NOT UNDERSTOOD isn’t just scientific negligence—it’s madness.

    Skeptic hit the nail on the head with his criticism of your mischaracterization of proper “placebo.” For example, you say: “A clinical placebo is a treatment that has no intended therapeutic effect.” But then you declare: “Vaccines often also have an extra added ingredient, called the adjuvant, which works as an immune enhancer. The adjuvant is sometimes included in the placebo formulation.” But… you already stated that a placebo should have no therapeutic effect—clearly, enhancing an immune response IS a therapeutic effect! This is the kind of acute logical contradiction that underpins a lot of commonly referenced vaccine science.

    In a previous comment, you also said: “I think it is fair to accept the general scientific consensus on the use of placebos in clinical studies because these are the standards that are globally accepted, adopted, and evaluated. This international consensus is arrived at by experience and reason.” This is another dangerous and unfounded assumption. Scientific consensus is a political construct and can be arrived at in many ways, not all of which rely strictly on experience, reason, objective data, or the scientific method. Regulatory agencies and public health institutions are full of human beings and their politics and assuming that their agendas align entirely with the interests of public health is extremely naive. Studies are cooked, protocols corrupted to ensure expedited regulatory approval, etc. Political pressure, conflicts of interest, regulatory capture, and a host of other unknowable variables can easily lead “scientific consensus” off the rails when billions in profits are at stake. You must consider the fallibility of human institutions when evaluating the quality of the science that they produce, and the pharmaceutical clinical trial and peer-review systems currently deserve a failing grade.

    Sorry to “drag you back in,” but frankly this article and the subsequent defenses thereof are a mess of illogical conclusions, presumptive value judgements, and pharmaceutical propaganda. Your readers deserve a competing point of view based on an objective analysis of all of the available information, rather than a regurgitation of conventional wisdom and unscientific assumptions that may muddy the waters and confuse people who are new to this particular discussion.

    To start: even “the most rigorous” vaccine trials are useless if they are poorly designed—as the old saying goes, “garbage in, garbage out.” Additionally, Helen’s opinion that the Gardasil placebos were “well-thought out” is just that—an opinion, largely based on an uncritical acceptance of scientific consensus, by her own admission. In fact there has been ample criticism of Gardasil’s clinical trial designs from many scientists and doctors all over the world (well summarized in the comments here previously by Skeptic). Here is an additional reference for these criticisms, which I suggest you read in its entirety:

    Also… here is another analysis of HPV vaccine trials, viewed through the lens of Cochrane’s recent meta-analysis. The author arrives at these conclusions:
    (1) No credible science supports the claims of health benefits from HPV vaccination at the population level, and
    (2) The risks of serious and moderate adverse events may be knowable via re-analysis of data submitted to the FDA for Gardasil 4-valent vaccine, and for the Gardasil 9-valent vaccine. However, at this time, no credible science exists that can support the conclusion that HPV vaccination is generally safe.

    The bottom line—you can produce all of the studies you want, but when your clinical trials are designed to hide rather than unearth safety data, they aren’t worth the paper they’re printed on. And if you’re not doing a deeper analysis of how these trials were designed and conducted—or you’re willing to accept the patently absurd idea that a true inert placebo isn’t necessary when conducting a vaccine safety trial for a product using a well known neurotoxin as an adjuvant (looking at you, Merck)—you simply do not have a leg to stand on when you blithely declare things like “vaccinated have better outcomes than unvaccinated.” Your data set is hopelessly corrupted from the get-go and you might as well abandon science and go grab a Stephen King novel, as you clearly prefer fiction to evidence-based scientific inquiry.

    • crd,
      Harsh criticism indeed. Like Grant I do not have half a life time to address all errors of fact and logic. However, here are a couple related to the ‘evidence’ provided.
      1. You criticise the design of the Gardasil trials and go on to suggest I read an article in Slate magazine written by someone who clearly does not understand the lifecycle of vaccine safety monitoring and has no background in vaccine science. In fact the article is so bad it uses anecdote to argue the case. This has no place in science. The author also failed to acknowledge the vast evidence on the matter. kind of an oversight really don’t you think? I am afraid magazine article by unqualified journalists do not constitute scientific evidence.
      2. You have linked me to someone’s blog or something that criticises a Cochrane meta-analysis (Not the Cochrane itself). The author James Lyons-Weiler appears to be a bit of a crank from what I can see and most certainly not a practicing scientist. The link repeats the usual pseudoscientific anti vaccine tropes about Gardasil. Lyons-Weiler rattles on about sero-type replacement. Hold up! Since when did sero-type replacement become an issue? Seems to be something this particular author lays claim to. In fact this author seems to do a lot of reinterpreting others work. I suggest he goes and does his own research then publishes it in a reputable forum to be judged. No this does not constitute scientific evidence crd.

  • You could spend half a lifetime trying to correct that lot 🙁

    There are plenty of websites and information sources to get this sort of stuff right. Here’s part of it the from IMAC website (PDF file):

    Formaldehyde is not an adjuvant. Any formaldehyde present would be trace amounts — tiny levels that have no effect. Our biology can handle a decent amount of formaldehyde, it has to because it’s making the stuff. For example, it’s a by-product when cells make DNA or some amino acids.

    As you can see, this is basic knowledge. The rest falls on the same sort of thing.

  • I‘m not sure I follow the logic… does that mean your’e all cool with testing the safety of pears using formaldahyde as a placebo? Isn’t that the converse of your analogy?

  • Paul,

    No, she wrote,

    testing the consumption of formaldehyde against placebo in order to establish the safety of an pear

    It’s your reading being out, not her writing!

    She wrote testing formaldehyde, not using it as a placebo, testing it against a placebo.

    (For those not familiar with the analogy, pears have a fair amount of formaldehyde, much more than vaccines. The analogy isn’t perfect. Analogies aside small amounts of formaldehyde are natural, even in the air. There are lots of other things with formaldehyde. If you must worry about it, you’re better worrying about getting it from heavily polluted air, cigarette smokers, etc., and industrial hazard for those working with materials that make it.)

    • Yep.

      Pears have about 60x more formaldehyde in them than a vaccine (there are some vaccine with residual formaldehyde in).
      I propose assessing the safety of pears, not by comparing a pear to a placebo, but by comparing formaldehyde with a placebo – after all, that is essentially what some people are advocating.

  • “In fact the article is so bad it uses anecdote to argue the case”

    What else could they do? This is about a company with a criminal history failing to track health problems during a safety study!!! which is incredibly shocking and unethical. Instead addressing it is dismissed as an anecdote.

    Do you want a RCT comparing how often they fail to register health problems? Seriously?

    I have come to the conclusion that anyone defending this knows well that the trial was flawed but they are so convinced that the follow up population studies must be sufficient and they could not be wrong that they simply pretend no flaws exist. It is a strong belief that they do not need a good RCT because they already know what the risks and benefits are.

    The truth is of course proper RCTs are needed. There is a reason why they exist.

    Basically they are making up excuses or dismiss anyone who question it as unsophisticated idiots and hide behind their redefinitions of what good science is.

    How sad and how arrogant. In this field science is dead I guess. Based on the same sloppy science they want to vaccinate every pregnant woman now.

    God help us.

  • It does read as if bigotry now stands in for science. Instead of reviewing the trial research relative to the TGA statement that Gardasil’s target age-group’s placebo was ‘misrepresented as saline’, Grant Jacobs has trawled the internet to find out my religious affiliation. I have no interest in his religion. It seems the moderator of this science blog also accepts bigotry. For the sake of religious literacy, Catholic Church schools all provide routine and complete Gardasil vaccination.
    When my research was first published I received many warnings to blazen over the internet that I was not suicidal. This seemed an extreme overraction at the time, but with the co-mingling of bigotry and intolerance replacing science, even on a science blog site, it becomes clear why other reserchers advised me so. No I am not and never have been suicidal, but presenting unpopular research does seem to invoke more than a scientific response, as evidenced here. Even scientists in this field resort to ad hominem attacks – itself informative of their approach.

  • No I read it fine. Even understood. Perhaps I wasn’t clear or have fallen victim to some logical fallacy I don’t understand. I was merely using the Professor’s analogy (pear = vaccine formaldahyde = adjuvant) to highlight the counterintuitiveness of testing a drug for safety using a potentially dangerous constituent of the drug as a placebo. That is what I can’t fathom despite reading this post at least fifty times. I asked the question that lead to this post. I bought Vaccine (the book you recommended months later) the same day I found this blog. I have tried hard to understand but I am at the stage where I pretty much have to concede to the anti-vaxer who I argued with about this that ahe wasrgument

  • Grr soz premature entering. “that she was right, I was wrong.

    Thankyou Professor for your time and expertise. I think this blog does provide an important resource and being able to ask questions is invaluable.

    Just an observation; generally I am comfortable with uncertainity and risk, I am more suspicious of those who make definitive statements that are contentious or unproven. Acknowledging the limits of science or our understanding is not always a negative. Best wishes.

  • Just to note that the recent Cochrane Collaboration review on HPV vaccines has been criticised by the Nordic group of Cochrane, with one main objection being that the review calls adjuvanted placebo a “placebo”.
    I am sure we will get some clarity on this when Cochrane Central respond.